DESCRIPTION
Vesicoureteral reflux (VUR) is the retrograde flow of urine from the bladder upward toward the kidney, most commonly seen in children. Although the exact prevalence of VUR in the general population is unknown, about one third of children with urinary tract infections (UTIs) are found to have VUR. In addition, there appears to be a genetic predisposition to VUR; therefore, children with UTI and their siblings often undergo evaluation for VUR. VUR is definitively diagnosed by voiding cystourography. The severity of reflux is described by a grading system, most commonly that of the International Reflux Study Group, which grades reflux from I to V.
The central management strategy of children with VUR has been avoidance of UTI-induced damage, either with antibiotic prophylaxis to sterilize the urine, or with surgical re-implantation of the ureters to correct the underlying reflux. Since VUR is known to spontaneously resolve, particularly in lower grades of reflux (i.e., grades I and II), the antibiotics are given continuously until resolution, while surgery is reserved as initial therapy for those with high-grade reflux (grades III and IV) or as salvage therapy for those who are either noncompliant with antibiotic therapy, have breakthrough UTIs while receiving prophylactic therapy, or those with low-grade reflux that does not spontaneously resolve.
Surgical management involves lengthening the intramural ureter by modification of the ureterovesical attachment with re-implantation of the ureters. Success rates for surgery are reported to be above 98% for reflux Grades III and IV; and about 80% for reflux Grade V. In addition to surgery-associated morbidity, obstruction and reoperation rates have been reported to be as high as 9%.
The use of bulking agents in the treatment of VUR has been investigated for over 20 years and has been suggested as an alternative to either antibiotic or surgical therapy. In a cystoscopic outpatient procedure, bulking agents can be injected around the ureteral orifices to minimize reflux.
The STING procedure (subureteral trans-urethral injection) involves the endoscopic injection of a bulking agent into the submucosal bladder wall just below the ureteral opening. In the more recently used modified STING procedure, the needle is placed in the ureteral tunnel and the bulking agent is injected into the submucosal intraureteral space. When successfully injected the compound tracks along the length of the detrusor tunnel and establishes a coapted ureteral tunnel.
A variety of agents have been used, ranging from collagen (e.g., Contigen®, Zyderm®, Zyplast®), polytetrafluoroethylene paste (Teflon®), polydimethylsiloxane (Macroplastique®), and dextranomer/hyaluronic acid copolymer (Deflux®).
Dextranomer/hyaluronic acid copolymer (Deflux®) is the only agent specifically approved by the U. S. Food and Drug Administration (FDA) for the treatment of children with VUR grades II-IV in the United States. The manufacturer voluntarily withdrew the copolymer product (e.g., Uryx®, Tegress™) from the market in December 2007.
POLICY
Periureteral bulking agents for the treatment of vesicoureteral reflux grades II-IV is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
The use of periureteral bulking agents for the treatment of vesicoureteral reflux in other clinical situations is considered investigational.
Policies with similar titles: Urethral Bulking Agents for Stress Urinary Incontinence
MEDICAL APPROPRIATENESS
Periureteral bulking agents for the treatment of vesicoureteral reflux grades II - IV, is considered medically appropriate if ALL of the following criteria are met:
Medical therapy has failed, (e.g. antibiotic prophylaxis to prevent urinary infections, bladder training medications such as anticholinergic drugs or surveillance for spontaneous resolution)
The individual is a candidate for a surgical procedure
IMPORTANT REMINDER
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
ADDITIONAL INFORMATION
A number of publications, mostly retrospective, have been published on the use of periureteral bulking agents for the treatment of VUR. A 2006 meta-analysis included 63 studies (3 randomized prospective, 7 prospective, 52 retrospective, and 1 study of unknown design) with a total of 5,527 patients. Interpretation of this meta-analysis is limited by the inclusion of a variety of bulking agents, some of which have since been abandoned due to low success rates, and by the large proportion of retrospective studies in which concerns exist about enrollment criteria and adequacy of follow-up.
Dextranomer/hyaluronic acid copolymer (Deflux®), a sterile, biodegradable gel, is the only agent specifically approved by the U. S. Food and Drug Administration (FDA) for the treatment of children with VUR grades II-IV in the United States.
No current randomized controlled studies were found in the published literature that validate the use of periureteral bulking agents as a treatment of vesicoureteral reflux if the condition is not amenable to surgical intervention.
SOURCES
Bae, Y. D., Park, M. G., Oh, M. M., & Moon, D. G. (2010). Endoscopic subureteral injection for the treatment of vesicoureteral reflux in children: Polydimethylsiloxane (Macroplastique®) versus Dextranomer/Hyaluronic AcidCopolymer (Deflux®). Korean Journal of Urology, 51 (2), 128-131. (Level 2 Evidence - Independent study)
Bauer, R., & Kogan, B. A. (2008). New developments in the diagnosis and management of pediatric UTIs. Urologic Clinics of North America, 35 (1), 47-58.
BlueCross BlueShield Association. Medical Policy Reference Manual. (10:2010). Periureteral bulking agents as a treatment of vesicoureteral reflux (7.01.102). Retrieved September 27, 2011 from BlueWeb. (22 articles and/or guidelines reviewed)
Chertin, B., Kocheroy, S., Chertin, L., Natsheh, A., Farkas, A., Shenfeld, O. Z., et al. (2011). Endoscopic bulking materials for the treatment of vesicoureteral reflux: A review of our 20 years of experience and review of the literature. Advances in Urology, 2011, 1-7.
Cooper, C. (2009). Diagnosis and management of vesicoureteral reflux in children. Nature Review, 6 (9), 481-489.
Elder, J. S., Diaz, M., Caldamone, A. A., Cendron, M., Greenfield, S., Hurwitz, R., et al. (2006). Endoscopic therapy for vesicoureteral reflux: A meta-analysis. I. Reflux resolution and urinary tract infection. The Journal of Urology, 175 (2), 716-722. (Level 1 Evidence - Industry study)
Greenbaum, L. A., & Mesrobian, H-G., O. (2006). Vesicoureteral reflux. Pediatrics Clinics of North America, 53 (3), 413-427.
Hayn, M., Smaldone, M., Ost, M., & Docimo, S. (2008). Minimally invasive treatment of vesicoureteral reflux. Urologic Clinics of North America . 35 (3), 447-488.
Hodson, E. M., Wheeler, D. M., Smith, G. H., Craig, J. C, Vimalachandra, D. Interventions for primary vesicoureteric reflux. Cochrane Database of Systemic Reviews 2007, Issue 3. Art. No. CD001532. DOI: 10.1002/14651858.CD001532.pub3.
Lackgren, G., & Stenberg, A. (2009). Endoscopic treatment of vesicoureteral reflux: Current practice and the need for multifactorial assessment. Therapeutic Advances in Urology, 1 (13), 131-141.
National Guideline Clearinghouse. (2010). Management of infants less than one year of age with vesicoureteral reflux. In: Management and screening of primary vesicoureteral reflux in children: AUA guideline. Retrieved September 26, 2011 from http://www.guidelines.gov.
National Guideline Clearinghouse. (2010). Management of vesicoureteral reflux in the child over one year of age. In: Management and screening of primary vesicoureteral reflux in children: AUA guideline. Retrieved September 26, 2011 from http://www.guidelines.gov.
National Guideline Clearinghouse. (2010). Screening of siblings and offspring of patients with vesicoureteral reflux in children. In: Management and screening of primary vesicoureteral reflux in children: AUA guideline. Retrieved September 26, 2011 from http://www.guidelines.gov.
National Guideline Clearinghouse. (2011). ACR appropriateness criteria® recurrent lower urinary tract infections in women. Retrieved September 29, 2011 from http://www.guidelines.gov.
U. S. Food and Drug Administration. (2001, September). Center for Devices and Radiological Health. Pre-market approval (PMA). Deflux injectable gel - P000029. Retrieved September 27, 2011 from http://www.accessdata.fda.gov/cdrh_docs/pdf/P000029b.pdf.
Winifred S. Hayes. Medical Technology Directory. (2007, December; last update search December 2010). Ureteral bulking agents for vesicoureteral reflux disease. Retrieved September 27, 2011 from www.Hayesinc.com/subscribers. (44 articles and/or guidelines reviewed)
Zaffanello, M., Franchini, M., Brugnara, M., & Fanos V. (2009). Evaluating kidney damage from vesico-ureteral reflux in children. Saudi Journal of Kidney Diseases and Transplantation, 20 (1), 57-68.
Zilberman, D., & Mor, Y. (2008). Has the data efflux regarding the promising outcome following injection of Deflux changed the management of adult vesicoureteral reflux? Advances in Urology, 2008, 1-5.
ORIGINAL EFFECTIVE DATE: 3/8/2007
MOST RECENT REVIEW DATE: 10/13/2011
ID_BA
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